Diabetic retinopathy is one of the leading causes of blindness and disability in the United States. One of the controversial issues in the treatment of diabetes is whether a regimen of strict control of blood glucose levels will delay the development and/or progression of the vascular complications of the disease. Recent technological developments have made possible the improvement of diabetic control to an extent not possible previously. Although such improved control has been shown to produce improvement in retinal function, some reports have suggested that the rate of progression of diabetic retinopathy may be increased. The main purpose of this study is to investigate the hemodynamic changes that occur in the retinal circulation when the usual level of diabetic control (mean blood glucose levels in a clearly hyperglycemic range) is changed into a strict diabetic control in which blood glucose concentration is in the normal or near normal range. For this purpose, we are investigating in insulin dependent diabetics, the retinal circulation and its regulatory response to pure O2 breathing just prior to the institution of strict metabolic control and then one week, two months and six months later. Retinal circulatory parameters are being measured using the following noninvasive techniques: Laser Boppler Velocimetry which provides measurements of the circulation in the main retinal vessels and Blue Field Simulation which enables the study of the retinal microcirculation in the macular areas. We are also investigating the relationship between the changes in the circulatory parameters and 1) changes in blood glucose levels: 2) changes in hemoglobin A1c levels; and 3) presence or absence of deterioration of retinopathy. We have performed this study in 9 subjects and we are currently investigating 4 additional ones. In this continuation grant we are proposing to finish our investigative protocol in a total of 30 diabetic patients. The results of this study may have important implications, both with regard to how we manage diabetic patients and our understanding of the pathogenetic mechanisms involved in diabetic retinopathy.